A Muscarinic Antagonist Reduces Airway Inflammation and Bronchoconstriction Induced by Ambient Particulate Matter in a Mouse Model of Asthma

• Published in: International journal of environmental research and public health Vol. 15; no. 6; p. 1189
• Main Authors: Kurai, Jun, Watanabe, Masanari, Sano, Hiroyuki, Iwata, Kyoko, Hantan, Degejirihu, Shimizu, Eiji
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06-06-2018; MDPI
• Subjects: Air pollution; Alveoli; Animals; Asthma; Asthma - chemically induced; Asthma - drug therapy; Asthma - pathology; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Bronchoconstriction; Bronchoconstriction - drug effects; Bronchus; Cytokines - analysis; Disease Models, Animal; Fluticasone; Formoterol; Health care; Inflammation; Interferon; Interleukin 13; Interleukin 5; Interleukin 6; Leukocyte Count; Leukocytes (eosinophilic); Leukocytes (neutrophilic); Lungs; Male; Medicine; Metabolites; Mice; Mice, Inbred BALB C; Mortality; Muscarinic Antagonists - pharmacology; Muscarinic Antagonists - therapeutic use; Outdoor air quality; Ovalbumin; Particulate emissions; Particulate matter; Particulate Matter - toxicity; Particulates; Patient admissions; Propionic acid; Reactive Oxygen Species - blood; Respiratory tract; Respiratory tract diseases; Studies; United States > US; Japan; airway inflammation; particulate matter; muscarinic antagonists; asthma; ovalbumin mouse model
• ISSN: 1660-4601; 1661-7827; 1660-4601
• DOI: 10.3390/ijerph15061189

Ambient particulate matter (PM) can increase airway inflammation and induce bronchoconstriction in asthma. This study aimed to investigate the effect of tiotropium bromide, a long-acting muscarinic antagonist, on airway inflammation and bronchoconstriction induced by ambient PM in a mouse model of asthma. We compared the effect of tiotropium bromide to that of fluticasone propionate and formoterol fumarate. BALB/c mice were sensitized to ovalbumin (OVA) via the airways and then administered tiotropium bromide, fluticasone propionate, or formoterol fumarate. Mice were also sensitized to ambient PM via intranasal instillation. Differential leukocyte counts and the concentrations of interferon (IFN)-γ, interleukin (IL)-5, IL-6, IL-13, and keratinocyte-derived chemokine (KC/CXCL1) were measured in bronchoalveolar lavage fluid (BALF). Diacron-reactive oxygen metabolites (dROMs) were measured in the serum. Airway resistance and airway inflammation were evaluated in lung tissue 24 h after the OVA challenge. Ambient PM markedly increased neutrophilic airway inflammation in mice with OVA-induced asthma. Tiotropium bromide improved bronchoconstriction, and reduced neutrophil numbers, decreased the concentrations of IL-5, IL-6, IL-13, and KC/CXCL1 in BALF. However, tiotropium bromide did not decrease the levels of dROMs increased by ambient PM. Though eosinophilic airway inflammation was reduced with fluticasone propionate, neutrophilic airway inflammation was unaffected. Bronchoconstriction was improved with formoterol fumarate, but not with fluticasone propionate. In conclusion, tiotropium bromide reduced bronchoconstriction, subsequently leading to reduced neutrophilic airway inflammation induced by ambient PM.